Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein–induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD.

Peritumoral edema impedes the full delineation of fiber tracts due to partial volume effects in image voxels that contain a mixture of cerebral parenchyma and extracellular water. The purpose of this study is to investigate the effect of incorporating a free water (FW) model of edema for white matter tractography in the presence of edema. We retrospectively evaluated 26 consecutive brain tumor patients with diffusion MRI and T2-weighted images acquired presurgically. Tractography of the arcuate fasciculus (AF) was performed using the two-tensor unscented Kalman filter tractography (UKFt) method, the UKFt method with a reduced fiber tracking stopping fractional anisotropy (FA) threshold (UKFt+rFA), and the UKFt method with the addition of a FW compartment (UKFt+FW). An automated white matter fiber tract identification approach was applied to delineate the AF. Quantitative measurements included tract volume, edema volume, and mean FW fraction. Visual comparisons were performed by three experts to evaluate the quality of the detected AF tracts. The AF volume in edematous brain hemispheres was significantly larger using the UKFt+FW method (p<0.0001) compared to UKFt, but not significantly larger (p = 0.0996) in hemispheres without edema. The AF size increase depended on the volume of edema: a significant correlation was found between AF volume affected by (intersecting) edema and AF volume change with the FW model (Pearson r = 0.806, p<0.0001). The mean FW fraction was significantly larger in tracts intersecting edema (p = 0.0271). Compared to the UKFt+rFA method, there was a significant increase of the volume of the AF tract that intersected the edema using the UKFt+FW method, while the whole AF volumes were similar. Expert judgment results, based on the five patients with the smallest AF volumes, indicated that the expert readers generally preferred the AF tract obtained by using the FW model, according to their anatomical knowledge and considering the potential influence of the final results on the surgical route. Our results indicate that incorporating biophysical models of edema can increase the sensitivity of tractography in regions of peritumoral edema, allowing better tract visualization in patients with high grade gliomas and metastases.

Intracranial hemorrhage (ICH) after traumatic brain injury (TBI) commonly increases in size and coagulopathy has been implicated in such progression. Our aim is to perform a meta-analysis to assess their relationship. Cochrane library, PubMed, and EMBASE were searched for literatures. Pooled effect sizes and 95% confidential intervals (CIs) were calculated using random-effects model. We included six studies, involving 1700 participants with 540 progressive hemorrhagic injuries (PHIs). Our findings indicate that PT, D-dimer level, and INR value are positively associated with the risk of PHI. Higher level of PLT and Fg seemed to suggest a lower risk of PHI. Among these parameters, higher D-dimer level and INR value would possess more powerful strength in predicting PHI.

Background: White matter injury (WMI) represents a significant etiological factor contributing to neurological impairment subsequent to Traumatic Brain Injury (TBI). CD36 receptors are recognized as pivotal participants in the pathogenesis of neurological disorders, including stroke and spinal cord injury. Furthermore, dynamic fluctuations in the phenotypic polarization of microglial cells have been intimately associated with the regenerative processes within the injured tissue following TBI. Nevertheless, there is a paucity of research addressing the impact of CD36 receptors on WMI and microglial polarization. This investigation aims to elucidate the functional role and mechanistic underpinnings of CD36 in modulating microglial polarization and WMI following TBI. Methods: TBI models were induced in murine subjects via controlled cortical impact (CCI). The spatiotemporal patterns of CD36 expression were examined through quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescence staining. The extent of white matter injury was assessed via transmission electron microscopy, Luxol Fast Blue (LFB) staining, and immunofluorescence staining. Transcriptome sequencing was employed to dissect the molecular mechanisms underlying CD36 down-regulation and its influence on white matter damage. Microglial polarization status was ascertained using qPCR, Western blot analysis, and immunofluorescence staining. In vitro, a Transwell co-culture system was employed to investigate the impact of CD36-dependent microglial polarization on oligodendrocytes subjected to oxygen-glucose deprivation (OGD). Results: Western blot and qPCR analyses revealed that CD36 expression reached its zenith at 7 days post-TBI and remained sustained at this level thereafter. Immunofluorescence staining exhibited robust CD36 expression in astrocytes and microglia following TBI. Genetic deletion of CD36 ameliorated TBI-induced white matter injury, as evidenced by a reduced SMI-32/MBP ratio and G-ratio. Transcriptome sequencing unveiled differentially expressed genes enriched in processes linked to microglial activation, regulation of neuroinflammation, and the TNF signaling pathway. Additionally, bioinformatics analysis pinpointed the Traf5-p38 axis as a critical signaling pathway. In vivo and in vitro experiments indicated that inhibition of the CD36-Traf5-MAPK axis curtailed microglial polarization toward the pro-inflammatory phenotype. In a Transwell co-culture system, BV2 cells treated with LPS + IFN-γ exacerbated the damage of post-OGD oligodendrocytes, which could be rectified through CD36 knockdown in BV2 cells. Conclusions: This study illuminates that the suppression of CD36 mitigates WMI by constraining microglial polarization towards the pro-inflammatory phenotype through the down-regulation of the Traf5-MAPK signaling pathway. Our findings present a potential therapeutic strategy for averting neuroinflammatory responses and ensuing WMI damage resulting from TBI. Graphical

Traumatic brain injury (TBI), a mainly lethal and highly debilitating condition, is increasing worldwide. However, the underlying mechanism has not been fully elucidated and effective therapy is needed. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in the cerebral cortex and hippocampus of rats, mice and human after TBI. lncRNAs may be associated with multiple pathophysiological processes following TBI and might play a crucial role in complications of TBI, such as traumatic optic neuropathy due to the regulation of specific signaling pathways. Some lncRNAs have also been found to be therapeutic targets for motor and cognitive recovery after TBI. lncRNAs may be promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. However, further research isneeded to clarify the underlying mechanisms and therapeutic effects of lncRNAs on TBI. We review the current progress of studies on lncRNAs in TBI to draw more attention to their roles in this debilitating condition.

Background:Paroxysmal sympathetic hyperactivity (PSH) is one of the important reasons for the high mortality and morbidity of traumatic brain injury (TBI). We aim to explore the role of the neutrophil extracellular traps (NETs) in the pathogenesis of sympathetic hyperexcitability after TBI and the underlying mechanisms, providing evidence for clinical treatment.Methods:Enzyme-linked immunosorbent assay was used to assess the plasma metanephrine and normetanephrine levels which represented the variation of the sympathetic system after TBI with rat diffuse axonal injury (DAI) model. NETs in the paraventricular nucleus (PVN) and circulating blood were examined using immunofluorescence and flow cytometry. Neutrophils-microglia co-culture system was established to further explore the effect of NETs on PSH and its mechanisms.Results:After TBI, metanephrine and normetanephrine levels began to increase at 9 h and peaked at 72 h. After the injury, the level of NETs kept increasing at 24 and 72 h in the PVN. A positive correlation was found between the concentration of the PVN NETs and blood catecholamine. Flow cytometry of peripheral blood cells revealed that NETs level in the injury group was higher than that in the control group. Immunofluorescence results confirmed the presence of NETs in the PVN after TBI. The positive result of immunoprecipitation suggested a correlation effect between LL37 and P2 × 7. Peptidyl arginine deiminase-4 (PAD4) inhibitor could inhibit the expression levels of MST1, YAP, and IL-1β. The hippo/MST1 pathway inhibitor could inhibit the expression levels of YAP and IL-1β.Conclusion:NETs formation in the PVN might be associated with sympathetic hyperactivity after TBI, which might relate to the activation of microglia cells and increased secretion of IL-1β via the hippo/MST1 pathway.